Chemotherapy with Aromatase Inhibitors and Breast Cancer

November 12, 2012

Hormonal therapy for treatment of breast cancer is the oldest and safest procedure for all phases of this cancer. Clinical studies indicate that hormonal therapies are an important component of adjuvant treatments and it also tends to prevent recurrence of cancer. Adjuvant treatments are therapies given in addition to primary therapy to increase the chance of disease free survival of postmenopausal breast cancer patients. Two drugs that are commonly used include tamoxifen and aromatase inhibitors (AIs). Tamoxifen’s mode of action involves blocking estrogen activity in the body where as AIs prevent the body from making estrogen thereby decreasing the amount of estrogen in the tumor halting progression of tumor cells. Tamoxifen has been used for more than twenty years and well tested in clinical trials. Generally, further hormonal treatments are required and the drug of choice has been non-selective AIs however, there has been some concern about its toxicity. More recently, selective AIs have been developed that have less toxicity. AIs come in two from: steroidal and non-steroidal. Clinical studies suggest that there may be clinical benefits when a non-steroidal AI is used first followed by a steroidal AI and vice versa.

The Journal of the National Cancer Institute (Aug. 22, 2011) published a report on AIs stating that toxicities associated with this drug may explain the lack o f survival improvement as compared to tamoxifen. AIs are an alternative to tamoxifen or administered after initial therapy with tamoxifen. The upshot is that AIs have demonstrated a decrease in breast cancer recurrence but not in improved survival.

The question here is, does aromatase inhibitors toxicity account for lack of improved survival? A meta-analysis of 7 trials involving over 30 thousand patients was conducted at the Princess Margaret Hospital in Toronto, Ontario comparing previous clinical trials that used AIs and tamoxifen.

The result of this meta-analysis was that AIs demonstrated an increase in heart disease and bone fractures but had lower rates of blood clots and cancer of the uterus. Apparently, there was no difference in risk of stroke or other types of cancer. Additionally, AIs used for two to three years after initial treatment with tamoxifen demonstrated a lower risk of death unrelated to breast cancer as compared to the use of either AIs or tamoxifen alone. These doctors concluded that toxicity of AIs when used for longer periods may explain the lack of overall survival benefit while still having a positive effect on breast cancer recurrence.

Basically, this analysis is showing that when aromatase inhibitors are used first there is no overall survival benefit however when tamoxifen is used first followed by AIs there is a reduction in AIs toxicity. So it seems that these coadjuvants provide a better balance between efficacy (producing the desired result) and toxicity. So, you have a compromise in trying to choose risks of breast cancer recurrence, drug toxicity and death.

The take home message is that post-menopausal patients with ER+ (estrogen receptor positive) metastatic breast cancer respond well with aromatase inhibitors at least as well as tamoxifen but perhaps a little better. Tamoxifen and aromatase inhibitors have basically the same survival rate, but this meta-analysis shows that AIs actually have lower toxicity overall when used as a second therapy.

This systematic study of the medical literature has brought to light that aromatase inhibitors have better efficacy and better toxicity profiles when used in second-line treatment than tamoxifen alone.